[Drug sensitivity in methotrexate-resistant choriocarcinoma cells: collateral sensitivity and cross resistance].
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Biomedical subjects
Publications and source records attributed to K Kanazawa.
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Activities of angiotensin-converting enzyme (ACE), other proteinases, and eosinophil chemotactic factor (ECF-G) are known to be elevated in hepatic hypersensitivity granulomas of thymus intact (nu/+) mice after Schistosoma mansoni infection. The enzyme activities also increase, but to a lesser degree in hepatic granulomas of athymic nude (nu/nu) mice, and ECF-G is not detectable. In this study isolated hepatic granulomas from nu/+ mice were grafted into the skin of uninfected nu/nu mice, and changes in those cellular functions were determined to examine whether the newly formed granulomas by recipient nu/nu cells acquire the functional activities as well as the histological appearance of nu/+ granulomas. ACE and ECF-G rapidly disappeared from grafted sites during the first 5 days, corresponding to loss of nu/+ cells from the graft. Reduction in activities of arylsulfatases, lysozyme, and acid phosphatase also occurred, but to a lesser extent. Recovery of ACE and ECF-G activities to the levels seen in nu/+ hepatic granulomas was observed by 14 days after grafting when nu/nu cells had accumulated in the grafts and formed new granulomas. Other enzymes increased to approximately half the levels seen in grafted donor granulomas. Circulating eosinophilia also increased. The findings indicate that nu/nu cells that accumulated in the skin grafts not only morphologically mimicked nu/+ type granulomas but also demonstrated nu/+ levels of cellular function. Analysis of skin granulomas developing in nu/+ mice after grafting of nu/+ hepatic granulomas showed the similar histology and enzymatic changes, whereas the skin sites inoculated with purified schistosome eggs alone caused neither significant histological changes nor elevation of ACE activity.
Preoperative patients with periampullary cancer had a higher mean sigma IRI value than that of normal controls, and also had a delayed pattern of insulin response and a lower insulinogenic index during oral-GTT. sigma IRI levels after pancreatoduodenectomy were similar to those of normal controls when the pancreatic remnants were histologically intact at the time of surgery. Postoperative sigma IRI levels could not be predicted based on the extent of histological fibrosis of the distal pancreas at the time of surgery. Patency of pancreatojejunostomy was obtained with the modified Warren's method in 39 out of 40 patients, and sigma IRI levels were maintained up to 5 years postoperatively. No significant difference was found in sigma IRI levels between pancreatoduodenectomised patients with the conventional Roux-en-Y procedure and those with the inverted Roux-en-Y with jejunal interposition. The mean insulin peak value and sigma IRI level were higher in pancreatoduodenectomised patients than in normal controls, and higher in gastrectomised patients than in pancreatoduodenectomised patients. Pancreatoduodenectomy with superior mesenteric arterial dissection resulted in remarkably low sigma IRI levels.
A 53 year-old Japanese woman with liver cirrhosis manifested massive hematemesis due to ruptured esophageal varices. Celiac angiography demonstrated an aneurysm of the splenic hilus and arteriovenous fistula around the aneurysm. She underwent splenectomy, proximal gastrectomy, distal esophageal devascularization and pyloroplasty. Histological examination of the aneurysm revealed arterial dysplasia with a focal medial gap. Microscopic tissue clefts at the site of a medial gap were considered to be the source of the angiographic arteriovenous fistula.
Although rare, mucinous cystadenocarcinoma of the pancreas is an established pathological entity. However, its characteristic features on diagnostic imaging have not yet been defined. Based upon clinicopathological studies on 5 cases, two subgroups of mucinous cystadenocarcinoma of the pancreas are proposed: the endophytic and the exophytic types. The former consist of large well-demarcated cystic tumors with numerous inward-growing cauliflower-like excrescences in mucinous material, which were characteristically demonstrated either by CT or ultrasonography. Tumors of this subtype were visualized as hypervascular masses in the capillary phase of angiography. Areas of malignant tissue were well-demarcated without capsular invasion, and tumors were free from lymph node or distant metastasis. Though cystic, the exophytic subtype had negligible inward-growing papillary projections. Corresponding to their macroscopic features, these tumors were demonstrated as cystic lesions lacking papillary projections on ultrasonography or CT. No tumor stains could be demonstrated by angiography. Despite of their smaller size than the former subtype, cancerous growth penetrated through the cyst wall and metastasized to lymph nodes, causing poorer prognosis than in the former.
The reaction products from butylated hydroxyanisole treated with nitrite under acidic conditions were investigated for mutagenic activity in Salmonella typhimurium his reversion assay and for DNA-damaging activity using H17 Rec+ (wild) and M45 Rec- (recombinationless) of Bacillus subtilis. The chloroform extract of the reaction mixture showed 9 spots on thin-layer chromatography (TLC). Compounds from 2 spots on the TLC had high mutagenic activity in TA100 without S9 mix, with DNA-damaging activity. The 2 mutagens were then crystallized from the reaction mixture and identified to be 2-tert.-butyl-p-quinone (t-BQ) and the dimer of t-BQ; 3,3'-di-tert.-butyl-biphenyldiquinone-(2,5,2',5') (BBDQ), from their instrumental analysis. The mutagenic activities of t-BQ and BBDQ were determined by Ames test, and the induced mutation frequencies were about 1.9 X 10(-4) (t-BQ) and 8.3 X 10(-5) (BBDQ).
Seventy-six patients with invasive hydatidiform mole (HM) were reviewed as to clinical course, particularly treatment and outcome, in relation to their age. The results were as follows: (i) metastatic cases showed approximately a twofold increase in patients over 40 compared with younger patients, (ii) more courses of chemotherapy were required to achieve a cure in patients over 40 than in younger patients and (iii) 4 of 19 patients (21.1%) over 40 developed choriocarcinoma, whereas none of younger patients did.
Hepatic granulomas of euthymic (nu/+) mice infected with Schistosoma mansoni were freeze-dried or freeze-thawed 3 times and transplanted subcutaneously into naive nu/+ and athymic (nu/nu) mice. The grafted sites, studied histologically, showed formation of organized granulomas in nu/+ mice similar to donor granulomas as observed after grafting of freshly isolated granulomas. On the other hand, in nu/nu mice, the nonviable transplants elicited small and disorganized granulomas, like hepatic granulomas in nu/nu mice with schistosomiasis, but different from fresh nu/+ transplants in nu/nu skin. The findings indicate viable cells are not required for transfer of granulomatous reactions, but T cells are needed for full expression.
A 63 year old Japanese man was admitted in Feb. 1983, with his chief complaint of upper abdominal pain. Physical examination showed only resistance in the right hypochondrium on palpation, but no icteric conjunctiva and skin. A large global tumor of the pancreas head was visualised as a hyperechoic mass with irregularly shaped cystic cavity in ultrasonography, as a hypervascular mass with lucent area in celiac arteriography, and as a mass lesion with low density area in body computerized tomography. Cancer cells were histologically confirmed on specimens taken by fine needle aspiration biopsy under ultrasonic guidance. Cancer of 6.5 X 6.0 X 4.0 cm in size was resected by pancreaticoduodenectomy. Four months after operation, two liver metastatic nodules were resected by right hepatic lobectomy. Histologically, tumor was composed of two characteristic patterns, acinar cell cancer and duct cell cancer, which were confirmed by immunohistochemical techniques. The patient is doing well 3 years and 3 months postoperatively without evidence of recurrent cancer. To our best knowledge, this case is the seventh of mixed ductal and acinar cancer in the world, but the previous 6 cases were reported on autopsy specimens.
Trophoblasts are divided into villous trophoblasts and extravillous trophoblasts, depending on whether they constitute a villous structure, and cell columns intervene between them. We conducted an immunohistochemical localization of human chorionic gonadotropin (hCG) alpha, hCG beta C-terminal peptide (CTP), human placental lactogen (hPL) and pregnancy-specific beta 1-glycoprotein (SP1) on the trophoblasts of normal human pregnancy, using forty-one hysterectomized pregnant uteri (6-22 weeks). In villous trophoblasts, the capacity to synthesize hCG alpha, hCG beta CTP, hPL and SP1 seemed to develop according to the morphological change from mononuclear cells to multinuclear cells. In contrast, the synthetic capacity of these proteins seemed not to correspond with the morphological change in extravillous trophoblasts: The location of hCG alpha, hCG beta CTP and SP1 was restricted to the mononuclear trophoblasts in the superficial decidua, while hPL was present extensively in extravillous trophoblasts, including multinuclear trophoblasts in the deciduomuscular junction. Therefore, it may be reasonably said that extravillous trophoblasts have many biological features distinct from villous trophoblasts and differentiate in an independent manner. Mononuclear trophoblasts in the cell column were negative for these proteins, which, together with morphological observations, strongly suggest the germinative nature of these cells.
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A phase II group study of cisplatin for cervical and endometrial carcinomas was carried out in 19 institutes throughout Japan. The patients entered consisted of 62 women with cervical and 7 with endometrial carcinoma of whom 39 and 4 were evaluable, respectively. Cisplatin was administered in either of two regimens; 10-20 mg/m2 i.v., on days 1-5, or 50-100 mg/m2 i.v., on day 1, every 3 to 4 weeks. The responders comprised 4 CRs and 10 PRs for cervical carcinoma and 1 CR and 2 PRs for endometrial carcinoma, and the response rates were 35.9% and 75.0%, respectively. The response rates by histological classification were 39.4% (13/33) for squamous cell carcinoma and 16.7% (1/6) for non-squamous cell carcinoma. Response rates analysed by lesion site were 33.3% for primary tumors, 36.8% for local lesions and 33.3% for metastases. Furthermore, the response rate among patients without any prior chemotherapy was 44.4% vs. 16.7% for those with prior chemotherapy. Adverse effects included nausea and vomiting (95.3%), anorexia (93%), anemia (72.1%), leucopenia (60.5%) and elevation of BUN (16.3%). Adverse effects were tolerable. We concluded from these results that cisplatin is among the most efficacious and useful drugs against cervical (and endometrial) carcinoma(s).
A 59 year-old female complained of right lower abdominal mass. She underwent radical operation 10 years ago for the right colonic cancer staged Dukes C. She had passed 10 years without any sign or symptom of recurrence. She noticed a egg-sized tumor in the right lower abdomen unexpectedly one month ago when she got a bruise on that region, and then the tumor grew rapidly. Preoperative examinations, including barium enema, abdominal computerized tomography and so on, suggested a extraluminal tumor with infiltration to the colon. Laparotomy revealed that the tumor originated from the right paracolic gutter. The tumor sized 18 X 11 X 8 cm was resected and histological diagnosis was adenocarcinoma with the similar structural pattern to the initial specimen. On the basis of both operations and histological findings, we concluded that free tumor cells might be implanted in the large raw surface of the right dorsolateral abdominal wall, which was created by surgical incision at the initial operation, and subsequently appeared as a local recurrence after 10 years interval.
Comparative cellular DNA content measurements have been done on two sites differing from each other in their anatomical location, in 16 cases of gastric cancer by means of microphotometry. In addition, comparisons on the DNA stemline of the original gastric lesions and their metastatic lesions (8 cases of liver metastases and 9 cases of lymph node metastases) also were done. The main stemlines in four cases (25%) out of 16 gastric cancers exhibited different main DNA stemlines from the other sites in the same lesion, although in the other 12 cases examined, two sites showed the same DNA stemlines to each other. In almost all cases, the DNA stemlines of the metastatic foci were consistent with those of the original lesions. The lymph node metastases simulated the original lesions in its DNA stemlines (89%) more than did the cases of livermetastases (63%). In an exceptional case, the original lesion exhibited two definite stemlines (2C & 3.5C), but only one (2C) was recognizable in the metastatic focus of the liver. This difference indicates the probable role of "clonal selection" in a blood-borne metastasis.
Radioactive secondary autoxidation products of linoleic acid were administered orally to rats and the incorporation of radioactive substances into lipids was investigated in the liver. The radioactive substances were significantly incorporated into hepatic mitochondrial and microsomal lipids 12 h after the administration. 80% of the radioactivity in mitochondria was detected in neutral lipids. The radioactivity in microsomal neutral lipids significantly decreased and the activity in phospholipids increased 12 h after the administration. On the other hand, contents of lipid peroxide and thiobarbituric acid reactive substances in liver were significantly increased by 40% at 15 h after the administration of the secondary autoxidation products. Activity of marker enzymes used for an indication of the hepatic injury was also elevated. Glutathione peroxidase activity increased 3-fold and catalase activity increased 1.5-fold. Activity of mitochondrial NAD-dependent aldehyde dehydrogenase, however, was decreased by 50%. It seems likely that the secondary autoxidation products orally administered are detoxified in the hepatic mitochondria, metabolized to neutral lipids, and further metabolized to phospholipids in microsomes, while as the incorporated secondary autoxidation products induces hepatic injury by lipid peroxidation.
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The mixed lymphocyte reaction (MLR)-blocking activity of sera was examined in patients with gestational choriocarcinoma. The frequencies of human leukocyte antigens (HLAs) in seven choriocarcinoma patients and their husbands were not different from those in the normal Japanese population. In patients who were successfully treated, many mismatches were found between the woman's HLA-A, B, C antigens and those of her spouse. Sera from three patients showed cytotoxic activity against their husbands' T lymphocytes. Similar results were obtained with sera absorbed with platelets to test for cytotoxic activity against the husbands' B lymphocytes. Cytotoxic activity sometimes disappeared at the recovery stage of the disease. Significant MLR-blocking activity was found in sera of patients in a tumor-bearing stage, but was absent 3-4 months after serum human chorionic gonadotrophin levels dropped into the normal range. It reappeared when patients relapsed, showing that MLR-blocking activity reflected tumor burden. The MLR-blocking factors in patients' sera may not be identical to the so-called serum nonspecific immune inhibitor factors, but was specific to, or dependent on, the use of the husbands' lymphocytes as stimulator cells and was mediated by immunoglobulin (antibodies) reactive with antigens expressed on the husbands' B lymphocytes, e.g. the MHC class II antigens.